Background

Depressive disorders are recurring and life-threatening conditions that affect approximately 120 million people worldwide. Of significant interest within the field of neuropsychiatric research is the development of valid animal models for depression to aid the understanding of the neurobiological and molecular mechanisms underlying depressive disorders. Various models of chronic stress have been used to induce symptoms in mice that are relevant to depression, among those are chronic unpredictable stress, foot-shock stress, immobilization stress followed by measurements of anhedonia or despair-like behaviors (e.g., sucrose preference test, forced swim test and tail suspension test), but they are not well validated as models of human depression (Krishnan and Nestler, 2011). Currently, chronic social defeat stress has been widely accepted as a well-validated model for depression, because of its reliability and reproducibility (Berton et al., 2006; Krishnan et al., 2007; Golden et al., 2011; Krishnan and Nestler, 2011; Russo and Nestler, 2013). The social defeat paradigm has been validated as a good model of human depression because of following reasons: 1) The depression phenotypes of susceptible mice (social avoidance, anhedonia, metabolic changes, etc.) are reversed by chronic treatment of anti-depressant drugs but not by acute administration. 2) Social defeat stress produces both a susceptible and resilient phenotype and this can be used to explain individual differences of human stress susceptibility in depression pathophysiology. 3) The susceptible phenotypes induced by social defeat stress are long lasting with concomitant genetic and epigenetic changes in the brain reward circuitry.